Spinal Processing of Descending Commands for Movement

描述(申请人提供)：拟议的实验将阐明在行为猴的颈髓中通过神经元间通路整合下行和感觉信号。这项工作的长期目标是了解脊髓回路对控制灵长类手臂正常和受损的自主运动的贡献。最终，这项工作将导致寻找可以克服与脊髓损伤和中风相关的运动障碍的疗法和干预措施。该项目的具体目标考察了两个广泛的问题。首先，脊髓神经元间通路整合下行和反馈信息来调节腕部和手部肌肉活动的幅度和时间的机制是什么？第二，脊柱通路中的信息处理如何使肌肉活动适应预期和意外的机械条件？清醒的猴子在不同的指令和不同的负荷条件下执行几个自愿的运动任务时，将记录C5-T1脊髓节段的中间神经元的活动。这些行为将包括手腕的弹道和缓慢跟踪运动，手的力量和精确握手，以及伸展和抓取任务。神经元的连通性将通过尖峰触发的肌肉活动平均值以及对外周传入和下行通路的自然和电刺激来识别。机械扰动将用于测试特定反馈通路对持续和代偿性肌肉活动的贡献。初级运动皮质的神经元将在同样的条件下进行研究。皮质和脊髓反应的比较将探索在执行随意的手臂和手运动过程中皮质脊髓处理的本质。 与公共健康相关：这些实验将为灵长类脊髓在手臂和手的各种准确和灵活动作的产生中的贡献提供新的见解。这些信息对于了解中枢神经系统损伤后运动损伤和恢复的脊椎机制是必不可少的。该项目将为未来研究可能的治疗方法或干预措施奠定基础，以促进中风和脊髓损伤的恢复。

DESCRIPTION (provided by applicant): The proposed experiments will elucidate the integration of descending and sensory signals by interneuronal pathways in the cervical spinal cord of the behaving monkey. The long-term objective of the work is to understand the contribution of spinal cord circuits to the control of normal and impaired voluntary movements of the primate arm. Ultimately, the work will lead to a search for therapies and interventions that can overcome the motor deficits associated with spinal cord injury and stroke. The specific aims of the project examine two broad issues. First, what are the mechanisms by which spinal interneuronal pathways integrate descending and feedback information to regulate the amplitude and timing of wrist and hand muscle activity during voluntary movements? Second, how does information processing in spinal pathways adapt muscle activity to expected and unexpected mechanical conditions? The activity of interneurons in the C5-T1 spinal segments will be recorded in awake monkeys performing several voluntary motor tasks with different instructions and under different loading conditions. These behaviors will include ballistic and slow tracking movements of the wrist, power and precision grips of the hand, and a reach-and-grasp task. The connectivity of the neurons will be identified with spike-triggered averages of muscle activity, and natural and electrical stimulation of peripheral afferents and descending pathways. Mechanical perturbations will be applied to test for the contribution of specific feedback pathways to ongoing and compensatory muscle activity. Neurons in primary motor cortex will be studied under the same conditions. Comparison of cortical and spinal responses will explore the nature of corticospinal processing during execution of voluntary arm and hand movements. PUBLIC HEALTH RELEVANCE: The experiments will provide new insights into the contribution of the primate spinal cord to the generation of a varied repertoire of accurate and flexible movements of the arm and hand. This information is essential for understanding spinal mechanisms of motor impairment and recovery following central nervous system injury. The project will lay the foundation for future studies on possible therapies or interventions to improve recovery from stroke and spinal cord injury.